Matrix-Assisted Laser Desorption Ionization (MALDI) on Time-Of-Flight (TOF) mass spectrometers is a powerful technique for extremely sensitive mass measurements of large biomolecules and synthetic polymers. Recently, it has been shown in our laboratories and by M. Mann et. al. at the EMBL, that Post-Source Decay (PSD) can yield additional fragmentation and structural information, for instance for glycopeptides, peptides and even small proteins, with excellent sub-picomole sensitivity and good mass accuracy.

Here we introduce two important advancements for structural TOF-MS. A novel type of high-resolution parent-ion preselector, e.g. for PSD on peptide mixtures, is presented with resolution >100, which eliminates appreciable attenuation and/or mass shifts in the PSD daughter ion spectrum and retains good accuracy (<0.5 Dalton). In addition, collision-induced dissociation (CID) is combined with PSD to obtain complementary information. For example, it is demonstrated that CID on the ACTH clip gives structurally very valuable immonium ion information, which greatly facilitates the structural analysis of higher mass fragments in the PSD spectrum of ACTH.